Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma

NCT03224767 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: A071601NCI-2017-00740U10CA180821
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 106

Brief Summary

This phase II trial studies how well vemurafenib and cobimetinib work in treating patients with BRAF V600E mutation positive craniopharyngioma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

BRAF V600E Mutation Present; Papillary Craniopharyngioma

Outcome Measures

Primary Outcomes (1)

• Response rate

  Defined as the number of responses achieved during treatment with BRAF and MEK inhibitors divided by the total number of evaluable patients and assessed by contrast-enhanced magnetic resonance imaging or computed tomography. Point estimates will be generated for response rates within each cohort with corresponding 95% binomial confidence intervals. Simon's two-stage design with one interim analysis for futility will be applied to evaluate response rate within each cohort.

  Up to 5 years

Secondary Outcomes (2)

• Progression-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Study Arms (1)

Treatment (vemurafenib, cobimetinib)

EXPERIMENTAL

Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.

Drug: Vemurafenib; Drug: Cobimetinib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Interventions

Vemurafenib DRUG

Given PO

Treatment (vemurafenib, cobimetinib)

Cobimetinib DRUG

Given PO

Treatment (vemurafenib, cobimetinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vemurafenib, cobimetinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Treatment (vemurafenib, cobimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* Pre-registration: Patients must have local diagnosis of papillary craniopharyngioma and have tissue slides available for submission to central pathology review; central pathology review will include immunohistochemistry (IHC) testing for BRAF V600E mutation (VE1 clone) and beta-catenin IHC (membranous, non-nuclear pattern) if needed to confirm diagnosis of papillary craniopharyngioma * Histologically proven papillary craniopharyngioma as documented by central pathology review with positive BRAF V600E mutation by IHC * Measurable disease and/or non-measurable disease * Measurable disease, defined as bidimensionally measurable lesions with clearly defined margins by magnetic resonance imaging (MRI) scans, with a minimum diameter of 10 mm in both dimensions * Progressive disease required in cohort B, defined as an increase in the bidirectional area by 25% within the past 13 months after surgery or radiation; progressive or recurrent disease is not required in cohort A, but is allowed provided it is a new diagnosis and patient has not received prior treatment. * Prior treatment * Cohort A: No prior therapy received other than surgery * Cohort B: Prior radiation therapy required (any type of prior radiation is allowed) * For patients treated with external beam radiation therapy, interstitial brachytherapy or radiosurgery, an interval of \>= 3 months must have elapsed from completion of radiation therapy to registration * Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity attributed to radiation with exception of alopecia, fatigue * For patients enrolling on Cohort A or Cohort B: * For patients treated with surgery, an interval of \>= 21 days must have elapsed prior to registration * No prior treatment with BRAF or MEK inhibitors * Steroid dosing stable for at least 4 days prior to registration * Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required * ECOG performance status =\< 2 * Comorbid conditions * No evidence of active bleeding, bleeding diathesis, or hemoptysis (\>= 1/2 teaspoon of red blood) =\< 8 weeks prior to registration * No evidence of intracranial hemorrhage =\< 4 weeks prior to registration * Patients who have experienced thromboembolic event within 6 months prior to registration must be on stable therapeutic anticoagulation for at least 4 weeks prior to registration * No symptomatic congestive heart failure (New York Heart Association class II, III, or IV) within 6 months prior to registration * No current unstable angina or uncontrolled arrhythmia * No uncontrolled hypertension at time of registration (blood pressure \[BP\] \> 150/95 despite antihypertensive therapy) * No known history of prolonged QT syndrome * No known history of ventricular arrhythmia within 6 months of registration * No known history of uveitis or iritis =\< 4 weeks prior to registration * No known history of or evidence of retinal pathology that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration within 12 months of registration * No known history of chronic lung disease * Concomitant medications * Chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors is not allowed; patients must discontinue the drug at least 14 days prior to study registration * Chronic concomitant treatment with CYP1A2 substrate is not allowed; patients must discontinue the drug at least 14 days prior to study registration * Absolute neutrophil count \>= 1500/mm\^3 * Platelets \>= 100,000/mm\^3 * Creatinine =\< 1.5 mg/dL OR creatinine clearance \>= 45mL/min * Bilirubin =\< 1.5 upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 ULN

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (106)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, 95603, United States

Location

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704, United States

Location

Mills-Peninsula Medical Center

Burlingame, California, 94010, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Cameron Park, California, 95682, United States

Location

Eden Hospital Medical Center

Castro Valley, California, 94546, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Palo Alto Medical Foundation-Camino Division

Mountain View, California, 94040, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Palo Alto Medical Foundation Health Care

Palo Alto, California, 94301, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, 95661, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94115, United States

Location

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, 94086, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Vacaville

Vacaville, California, 95687, United States

Location

Sutter Solano Medical Center/Cancer Center

Vallejo, California, 94589, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, 83605, United States

Location

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814, United States

Location

Idaho Urologic Institute-Meridian

Meridian, Idaho, 83642, United States

Location

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, 83687, United States

Location

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, 83854, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Central Care Cancer Center - Garden City

Garden City, Kansas, 67846, United States

Location

Central Care Cancer Center - Great Bend

Great Bend, Kansas, 67530, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Bronson Battle Creek

Battle Creek, Michigan, 49017, United States

Location

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

Location

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, 49503, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49048, United States

Location

Trinity Health Muskegon Hospital

Muskegon, Michigan, 49444, United States

Location

Corewell Health Lakeland Hospitals - Niles Hospital

Niles, Michigan, 49120, United States

Location

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, 49444, United States

Location

Corewell Health Reed City Hospital

Reed City, Michigan, 49677, United States

Location

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085, United States

Location

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

University of Michigan Health - West

Wyoming, Michigan, 49519, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Minnesota Oncology - Burnsville

Burnsville, Minnesota, 55337, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Fairview Clinics and Surgery Center Maple Grove

Maple Grove, Minnesota, 55369, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Saint John's Hospital - Healtheast

Maplewood, Minnesota, 55109, United States

Location

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Health Partners Inc

Minneapolis, Minnesota, 55454, United States

Location

Monticello Cancer Center

Monticello, Minnesota, 55362, United States

Location

North Memorial Medical Health Center

Robbinsdale, Minnesota, 55422, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Saint Francis Regional Medical Center

Shakopee, Minnesota, 55379, United States

Location

Lakeview Hospital

Stillwater, Minnesota, 55082, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, 55125, United States

Location

Central Care Cancer Center - Bolivar

Bolivar, Missouri, 65613, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

Location

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States

Location

Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States

Location

Great Falls Clinic

Great Falls, Montana, 59405, United States

Location

Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

Community Medical Center

Missoula, Montana, 59804, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07101, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Cancer Centers of Southwest Oklahoma Research

Lawton, Oklahoma, 73505, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Farmington Health Center

Farmington, Utah, 84025, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

South Jordan Health Center

South Jordan, Utah, 84009, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

FHCC South Lake Union

Seattle, Washington, 98109, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

United Hospital Center

Bridgeport, West Virginia, 26330, United States

Location

West Virginia University Healthcare

Morgantown, West Virginia, 26506, United States

Location

Camden Clark Medical Center

Parkersburg, West Virginia, 26101, United States

Location

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Cancer Center of Western Wisconsin

New Richmond, Wisconsin, 54017, United States

Location

Welch Cancer Center

Sheridan, Wyoming, 82801, United States

Location

Related Publications (2)

• Brastianos PK, Twohy E, Geyer S, Gerstner ER, Kaufmann TJ, Tabrizi S, Kabat B, Thierauf J, Ruff MW, Bota DA, Reardon DA, Cohen AL, De La Fuente MI, Lesser GJ, Campian J, Agarwalla PK, Kumthekar P, Mann B, Vora S, Knopp M, Iafrate AJ, Curry WT Jr, Cahill DP, Shih HA, Brown PD, Santagata S, Barker FG 2nd, Galanis E. BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas. N Engl J Med. 2023 Jul 13;389(2):118-126. doi: 10.1056/NEJMoa2213329.

  PMID: 37437144 DERIVED

• Rutenberg MS, Rotondo RL, Rao D, Holtzman AL, Indelicato DJ, Huh S, Morris CG, Mendenhall WM. Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study. J Neurooncol. 2020 Apr;147(2):387-395. doi: 10.1007/s11060-020-03432-9. Epub 2020 Feb 21.

  PMID: 32086697 DERIVED

MeSH Terms

Conditions

Craniopharyngioma

Interventions

Vemurafenib; cobimetinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Priscilla K. Brastianos, MD

  Massachusetts General Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 21, 2017
• Study Start: January 5, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: February 18, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (106)